Method of sugar coating tablets

ABSTRACT

TABLET CORES CONTAINING MEDICAMENTS, PARTICULARLY, HYGROSCOPIC MEDICAMENTS ARE COATED BY APPLYING DIRECTLY THERETO SUGAR SYRUP CONTAINING A SUCROSE HIGHER FATTY ACID ESTER WITHOUT APPLYING WATER PROOF COATING OR OTHER SUBCOATING TREATMENT.

United States Patent 3,639,564 METHOD OF SUGAR COATING TABLETS RyuichiKawata and Hiroitsu Kawada, Tokyo, Tadayoshi Ohmura, Niiza, and SumioUematsu, Urawa, Japan,

assignors to Yamanouchi Pharmaceutical Co., Ltd.,

Tokyo, Japan No Drawing. Filed Nov. 16, 1970, Ser. No. 90,105

Int. Cl. A01n 17/00; A61k 9/00 US. Cl. 42435 6 Claims ABSTRACT OF THEDISCLOSURE Tablet cores containing medicaments, particularly,hygroscopic medicaments are coated by applying directly thereto sugarsyrup containing a sucrose higher fatty acid ester without applyingwater proof coating or other subcoating treatment.

The present invention relates to a method of coating unpretreated tabletcores directly with sugar syrup containing a sucrose higher fatty acidester.

More particularly, the invention relates to a method of directly sugarcoating tablet cores using sugar syrup containing at least onemonoester, diester, or triester of sucrose and a higher fatty acidhaving 8-20 carbon atoms such as palmitic acid or stearic acid, saidester or ester mixture having a hydrophile lipophile balance (HLB) ofless than 11.

In the administration of medicaments and particularly pharmaceuticaltablets which are orally administered, to minimize any taste, improvetheir appearance, and minimize or prevent degradation of the activetherapeutic material exposed to high temperature and high humidity whilealso attempting to minimize damaging the tablet, the usual procedure indealing with the aforesaid problems has been to apply sugar coating tothe tablets.

In conventional sugar coating techniques, it is necessary that the edgesand corners of tablet cores be covered or rounded before the finishingsugar coating is applied. This has been done generally by applying anadhesive coating using a composition usually consisting of gelatin,acacia, sugar and water followed by a subcoating powder which rounds offthe tablet cores. This subcoating powder is usually a blend of insolublepowders, adhesive powders and lubricants. A typical subcoating powdercontains calcium carbonate, talc, kaolin, sugar, acacia, lactose, etc.The application of the subcoating powder requires a high degree of skilland is the most difiicult step of the entire sugar coating operation. Itis particularly important for the subcoating layers to be built upevenly and to be dried thoroughly. It will therefore be appreciated thata satisfactory and effective coating over the sharp edges of the tabletsis quite difficult to obtain and a large number of individual coatingsare required. In ordinary subcoating operations, the time required forbuilding up a suitable subcoating varies greatly according to the skillof the individual coating operator.

Now, when the medicaments present in tablet cores to be sugar coated arehighly hygroscopic, and are also easily susceptible to chemical orphysical degradation, it is impossible to apply sugar coating to suchtablets by usual conventional procedures without applying the subcoatingand hence it is required to form a preliminary water proof coating usinga water proofing material in addition to the involved pre-treatmentdescribed above. Obviously, such a precoating in addition to thepretreatment procedure described above results in a highly involved andtime consuming procedure which is most undesirable from an economicpoint of view. Moreover, when the thickness of the water proof coatingis increased Patented Feb. 1, 1972 "ice in order to provide a sufficientantihygroscopic and water proofing effect, the tendency of the tabletsto disintegrate is reduced resulting in an excessive period of timewhich is required to disintegrate the active material in the digestiveorgans. On the other hand, when the thickness of the water proof coatingis reduced for improving the disintegrating property, the medicamentsabsorb moisture readily during the subcoating and sugar coating as wellas after the sugar coating is finished, resulting in degradation ordamage to the medicament material.

An object of the present invention is to apply sugar coating directly totablet cores containing particularly hygroscopic medicaments therebyavoiding such conventional pretreatment steps as water proof coating andsubcoating.

Another object of this invention is to provide a coating compositionsuitable for sugar coating of tablet cores containing hygroscopicmedicaments.

A further object of this invention is to apply to tablet cores a stable,sugar coating which causes neither cracks nor degeneration ofmedicaments by the penetration of moisture during the sugar coating stepand after the sugar coating is finished and also causes no exudation ofthe medimaments material from the inner portion of the tablets.

Still another object of this invention is to apply a sugar coatinghaving good antihygroscopic property in a considerably shorter period oftime than is required in conventional sugar coating methods.

It has been discovered that when a sugar syrup containing at least onemonoester, diester or a triester of sucrose and a higher fatty acidhaving 8-20 carbon atoms which is prepared by the method disclosed inUS. Pat. 1,959,590 and this syrup is applied to tablets, quitesurprisingly, moisture does not diffuse into the inner portion of thetablet cores. That is, when tablet cores are immersed in the coatingcomposition used in this invention, after withdrawing the tablet cores,the coating compositions attached to the tablet cores are wiped away,and the weight of the tablet cores is measured, almost no increase ofweight is observed. On the other hand, when a coating compositioncontaining no sucrose higher fatty acid ester is used, the tablet coreimmersed in the coating composition absorbs water and collapses.

Therefore, according to the present invention, a sugar coating can bedirectly applied to tablet cores without applying water proof coatingeven if the medicaments contained in the tablet cores are unstable inthe presence of water. Also, in the present invention, sugar coating canbe applied effectively to such tablet cores containing medicaments whichare unstable in the presence of water without requiring subcoating whichis not only technically difficult to apply, requires great skill, butalso requires usually a longer period of time.

The pharmacutical tablets thus prepared have good antihygroscopicproperties; they can be stored without causing the degeneration of themedicaments in the tablets and cracking of tablets, and also they can bestored for a long period of time without reducing the breaking propertyof the tablet.

It is known that a sugar higher fatty acid ester is used for emulsionsof medicines; or the ester is added to a non-aqueous coating compositionor such as ester can be used in aqueous and non-aqueous coatingcompositions in coating of tablets (Japanese patent publication Nos.3787/65 now Japanese Patent 456,410 and 1 1845/62) now Japanese Patent305,633. However, until the present invention, the addition of a higherfatty acid ester to a simple sugar syrup for sugar coating was notknown. Moreover, the advantages and surprising results attributable tothe use of such a coating were most unexpected.

The shape of the tablet cores to be coated according to the presentinvention can vary and may be in disc form, doughnut form, a pelletform, a pill form, or a spindle form.

The coating syrup used in the present invention may be prepared asfollows: by dissolving or dispersing uniformly sugar and a sucrosehigher fatty acid ester in an amount of less than 30% by weight,preferably less than by Weight to the sugar in Water; warm water ispreferably used. The sucrose higher fatty acid ester has an HLB of lessthan 11 and preferably less than 7.

In the preparation of the coating syrup, a coloring agent, a tastingvehicle, a flavoring vehicle, shielding agent, and an extender which areusually used in a conventional sugar coating process may be added ifnecessary.

The coating syrup thus prepared may be applied to tablet cores byrepeating the application and drying of the syrup using the ordinarysugar coating procedure and in this case a high degree of skillgenerally required in a subcoating procedure is unnecessary, i.e.,dropping or spraying of the syrup on the tablet cores in the coating panand drying. Also, the thickness of the sugar coating may be desirablydetermined on considering the size of the tablets, the properties of themedicaments contained in the tablet cores, etc.

The sugar-coated tablets prepared by the process of this invention aresubstantially resistant to the formation of cracks, the occurrence ofexuding, etc., under severe conditions of high temperature and highhumidity not only during the coating steps but also after thepreparation of the coated tablet. Further, there is no change in thetime required for disintegration of the tablets after swallowing evenafter such tablets are stored for an extended period of time as comparedwith conventional sugar-coated tablets which are prepared by applyingsugar coating after applying a water proof coating and a subcoatingaccording to the usual techniques.

The invention will be illustrated by the following nonlimitativeexamples.

EXAMPLE 1 Composition: G. Sugar 9 50 Sucrose distearate 1 75 Water 450 rKNitto ester S-770, trade name, made by Dninippon Seito Procedure-Afterheating 450 g. of water above 80 C., 950 g. of sugar and then 75 g. ofsucrose distearate having an HLB of 7 were added slowly to the water,with stirring, to provide a homogenous coating composition. In a coatingpan were placed 10,000 tablet cores each weighing 150 mg. and whilerotating the coating pan, about g. of the coating composition preparedabove was applied onto the tablets. The coated tablet cores were thendried, in air at a temperature of about 50 C. By repeating the sameprocedure, sugar coated tablet cores each weighing 300 mg. wereobtained.

EXAMPLE 2 Composition: G. Sugar 950 Sucrose distearate 50 Talc 75 Water500 Procedure.After heating 500 g. of water to 90 C., 950 g. of sugar,50 g. of the sucrose distearate used as in Example 1, and 75 g. of talcwere added to the water, with stirring, to provide a homogenous coatingcomposition. By repeating the same procedure as in Example 1, about10,000 tablet cores each weighing 150 mg. were obtained; sugar coatedtablets each weighing 230 mg. were obtained.

4 EXAMPLE 3 Composition: G. Sugar 950 Sucrose mono, distearates 1 50Water 450 I kNitto ester S1170, trade name, made by Dainippon SeitoAfter heating 450 g. of water above C., 950 g. of sugar and 50 g. ofsucrose mono, distearates having an HLB of 11 containing about 50%mono-ester, 30% diester and about 20% tri-ester were added slowly to thewater, with stirring, to provide a homogenous coating composition.Following the procedure of Example 1, about 10,000 tablet cores eachweighing mg. were obtained; the sugar coated tablets each weighing 300mg. were obtained.

EXAMPLE 4 Composition: G. Sugar 950 Sucrose distearate 50 Titanium oxide10 Tartrazine aluminum lake 10 Water 500 After heating 500 g. of waterabove 90 C., 950 g. of sugar and then 50 g. of the sucrose distearate asin Example 1 were slowly added to the water, with stirring, and then 10g. of titanium oxide and 10 g. of tartrazine aluminum lake wereuniformly dispersed in the solution to provide a homogeneous coatingcomposition. Following the procedure of Example 1 about 10,000 tabletcores each weighing 150 mg. were obtained; the sugar coated tablets eachweighing 300 mg. were obtained.

EXAMPLE 5 Composition: G. Sugar 340 Sucrose distearate 25 Talc 25Tartrazine 1 Water 109 After heating 109 g. of water above 90 C., 340 g.

of sugar and then 25 g. of sucrose distearate and 25 g. of talc, as inExample 1, were slowly added to the water, with stirring, and then 1 g.of tartrazine was uniformly dispersed in the solution to provide ahomogeneous coating composition. Following the procedure of Example 1about 10,000 tablet cores each weighing 150 mg. were obtained; sugarcoated tablets weighing mg. were obtained.

The following experimental tests confirmed the excellent resultsattributable to the present invention.

Specimen: The sugar-coated tablets prepared by the method of Example 2.

Control specimen: The sugar-coated tablets prepared by applying waterproof coating of shellac to tablet cores and then applying a coating ofa mixture of sucrose, a binder and a suspensible powder thereto.

The following tests were applied to 100 tablets of each of the specimensand the control specimens and the results are shown in Tables 1-3.

Test 1 TABLE 1 Days stored 15 30 60 Specimen 0 0 0 Control specimen- 0100 100 Test 2 After storing at a temperature of 45 C. and a relativehumidity of 74%, the number of the cracked tablets was detected. Theresults are shown in Table 2.

TABLE 2 Days stored 30 60 Specimen 0 Control specimen". 25 100 Test 3After storing for 20 days at a temperature of 45 C. and a relativehumidity of 40-60%, the disintegration time (in minutes) of the tabletswas measured by using artificial gastric juice according to the U5.Pharmacopoeia (U.S.P. XVII) and the mean value was calculated. Theresults are shown in the following table.

TABLE 3 Days stored 0 20 Specimen. 12 14 Control speeimem- 25 40 free oftendencies to crack and to retard disintegration time consistingessentially of an aqueous sugar syrup and an effective water-proofingand anti-hygroscopic quantity of a sucrose 8 to 20 carbon atom higherfatty acid mono-, dior tri-ester having a hydrophile-lyophile balance ofless than 11.

2. A tablet according to claim 1 wherein sugar coating syrup colorants,opaquing agent, flavors and mixtures thereof are added.

3. A tablet according to claim 2 wherein a tartrazine aluminum lakecolorant and tri-ox'ide opaquing agent are added.

4. A tablet according to claim Lwherein the fatty acid ester is derivedfrom stearic acid.

5. A tablet according to claim 1 wherein the fatty acid ester is amixture of the mono-, diand tri-esters of stearic acid.

6. A tablet according to claim 1 wherein the fatty acid ester is derivedfrom a mixture of stearic and plamitic acids.

References Cited UNITED STATES PATENTS 2,893,990 7/1959 Hass et al.260-234 3,931,802 4/1960 Touey et al. 260-234 2,948,717 8/1960 Babayanet a1. 260-234 3,057,743 10/1962 Touey et al. 106-162 X 3,108,977 10/1963 Wolff 260234 X 3,160,565 12/1964 Duell 260147 3,495,998 2/1970Reeves et a1. 106-462 X SHEP K. ROSE, Primary Examiner US. Cl. X.R.

